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All in the (scientific) family

On a mild summer morning, three professors sit in a cramped office on Colorado State's campus. They talk about children's swim-team practice and home remodeling. One of the women shows off a skinned knee and warns of the dangers of quick bike turns on gravel.

Jennifer Nyborg, Karoline Luger, and Laurie Stargell are collaborating to study the inner workings of genes in DNA strands.

Renowned biochemists

But when the topic turns to work, it’s clear these dedicated researchers are involved in something much more complex. They become animated when discussing acetyltransferases and histone chaperones. Their eyes sparkle when speaking of macromolecular assemblages.

True to their teaching passion, these renowned biochemists are excited when explaining their research and a $7.8 million grant they recently received from the National Institutes of Health.

The prestigious five-year grant will allow a team of researchers to study the inner workings of genes in DNA strands and, hopefully, make important discoveries about the most basic building blocks of life. Jennifer Nyborg; Karolin Luger, a University Distinguished Professor; and Laurie Stargell will investigate how chromosomes untangle within DNA to expose genes that dictate cell behavior. Jeffrey Hansen is coinvestigator for the three projects within the grant.

How genes are turned on and off

“The question we’re asking is very fundamental to life, and the environment here at CSU and in the Department of Biochemistry and Molecular Biology gives us a significant edge,” says Nyborg, principal investigator on the NIH grant. “We’re studying genes and how they are turned on and off. It’s not why your eyes are blue, it’s how you have blue eyes and not green eyes.”

In every living cell, bulky proteins must maneuver through densely packed nucleosomes to access the genes so DNA can be copied – first into RNA and then into protein. That process occurs in thousands of genes in every cell of our bodies and results in giving each cell its unique instructions – for example, telling a liver cell how to be a liver cell and not a brain cell.

But scientists have limited understanding of how cells gain access to individual genes that are tightly compacted into chromosomes.

Long-standing mystery

“We know that nucleosomes serve to compact DNA to fit into a cell nucleus; what remains a long-standing mystery is how genes – encoded by the DNA – are unwound from the nucleosomes to allow access for copying their instructions into proteins and with a specific biological outcome for the cell,” Nyborg says.

“The cell faces an enormous paradox: It must tightly wrap the DNA around nucleosomes for compaction, but at the same time, it must unwrap the DNA at specifi c sites to turn a gene on.”

The key to this process is manipulating nucleosomes. Cells must strategically move or remove nucleosomes from DNA to gain access to underlying genes.

Team of investigators includes students

The team of investigators, which will include the three professors, Hansen, and up to 15 postdoctoral students, graduate students, technicians, and undergraduate students, will work on three research projects to discover more about how genes function in their densely packed intracellular environment.

Nyborg will tackle basic biochemistry that will reveal how nucleosomes are taken apart to expose the DNA of the gene. Luger’s experiments will focus on proteins that facilitate the assembly and disassembly of the nucleosome on the DNA. Stargell, whose specialty is yeast genetics, will study the movement of nucleosomes when genes are turned on in living cells.

The research being done by the three biochemists is unique, and so is their working relationship.

“By and large, most science is not done this way,” Nyborg says. Often, researchers work on their own, not sharing results until after publication. Nyborg adds that it’s unusual for one department to have such a concentration of expertise. “This research really does fi t well with the expertise we have in this department. The experts we need are right here.”

“We have a collaborative spirit,” says Stargell, who notes that just because they communicate well doesn’t mean they always agree. “We are fierce about our own projects. We argue a lot.”

Environment of collaboration

The women all credit CSU and the College of Natural Sciences for fostering an environment of collaboration. “CSU is more conducive to this than other institutions,” Luger says. “We’re encouraged to be collegial and collaborative, and it doesn’t have to be a dog-eat-dog world.”

Nyborg, Luger, and Stargell have high hopes for discoveries during their research, but they’re grounded in knowing that their work is a small piece of a large puzzle.

“It’ll open new questions,” Luger says. “That’s the nature of science. You poke something, and something else happens. But if you want to be a car mechanic, you have to know how a car works.”